Field of Inventive Subject Matter
The inventive subject matter relates to compounds of Formula I, compositions thereof, and processes for making such compounds as further described herein. The inventive compounds and compositions have antimicrobial properties and are useful as environmental disinfectants, topical cleansers such as topical personal care compositions, sanitizers, preservatives, in water treatment, as permanent or erodible coatings for medical devices and appliances, and in therapeutics. Additionally, the compounds of Formula I will serve as synthetic intermediates for making additional novel derivatives of triscationic amphiphile compounds, such as dimers of compounds of Formula I, other polymers of compounds of Formula I, and dimers and other polymers of compounds of Formula I dimerized or polymerized with other triscationic amphiphile compounds.
Background
Over the last few decades, the overuse of antibiotics and antimicrobial compositions has decreased their effectiveness, contributing to bacterial acquired resistance. In addition, the production of novel antimicrobials continues to decrease due to low financial return. This decline in the development of novel antimicrobials, combined with the misusage and over prescription of antibiotics, has contributed to the increasing prevalence of antimicrobial-resistant infections (ARIs), especially in the hospital setting. ARIs have contributed to more than 25,000 deaths in member states of the European Union, Iceland, and Norway and 23,000 deaths in the United States. Hospitals and nursing homes are particularly prone to harboring antimicrobial-resistant organisms due to the frequent use of antimicrobial agents and influx of infected patients.
Limiting the transmission of bacteria between individuals and contaminated equipment is critical to reducing or preventing hospital-acquired infections and reducing mortality rates for patients and those that come into contact with them. Further, the development of biofilm contaminations on hospital surfaces such as urinary catheters, central venous catheters, and dental syringes is also a growing concern.
The development of effective novel disinfectants, antimicrobial coatings, topical treatments for infections, and antimicrobial drugs are all highly desirable solutions to these problems and are expected to reduce the transmission of pathogens, decrease the risk of infection by antibiotic resistant organisms, and provide new therapeutic treatments.
The antimicrobial activity of cationic amphiphiles—compounds with hydrophobic and positively charged hydrophilic regions—was first reported in 1935 Amphiphiles continue to be utilized as antimicrobial agents in detergents, disinfectants, cosmetics, and other common household products. A large variety of novel amphiphiles has been synthesized in an effort to increase antimicrobial effectiveness and specificity.